The peritoneal dialysis has been applied as an effective therapy for end stage renal disease patients. The dialysis is proceeded by infusing dialysate into peritoneal cavity through a catheter, which is implanted in the patient's peritoneal cavity, and storing it for a certain period, thence withdrawing the dialysate out through the catheter. This procedure is repeated a few times every day.
This dialysis has a few advantages over hemodialysis in physiological point of view, as it purifies blood continuously through the patients' peritoneum, while hemodialysis purifies blood though an artificial membrane intermittently. Also peritoneal dialysis enables the patients' social activity, so that the peritoneal dialysis has been widely applied.
In hemodialysis, removal of excess liquid is achieved by raising the pressure of blood line over that of the dialysate line. However the same means can not be applied to peritoneal dialysis, therefore an osmotic agent is added into the dialysate so as to raise the osmotic pressure of the dialysate over that of plasma. The dialysate is infused into the peritoneal cavity to contact to peritoneum for removing excess liquid from the patient's body. For this purpose, glucose has been used as an osmotic agent. Glucose had been recognized to be safe and physiological, and to cause no problem on metabolism after it is absorbed into the body.
However, adverse effects were recognized as serious problems, such as disfunctioning of peritoneum, due to the absorption of large quantity of glucose into the patient body and the reaction with amino acids, peptide and protein, followed by the formation of AGEs, progress of collagen synthesis, and cross linking of protein. Consequently it causes peritoneum sclerosis and leads to cease of the therapy.
The cross linking reaction of protein molecules with glucose is assumed to take place as follows;

Carbonyl residue(s) containing sugars, such as glucose and the like, react with amino acids, peptides or protein (II), and through Shiff base (III) and Amadori compounds (IV), lead to advanced glycation end products (AGE); the cross linking between protein molecules
Also it has been reported that glucose is converted through dialysate sterilization process under high pressure and temperature to the following compounds, that is called glucose degradation products (GDP);
glyoxal,
methylglyoxal
3-deoxyglucosone.
The above-described GDPs are more reactive substances for AGE formation compared to sugars per se. When dialysate contains the GDPs, the protein cross linking reaction is accelerated by a few dozen to a few thousands times as fast as when the dialysate contains glucose alone.
An example of protein cross linkage formed in AGEs by the reaction between carbonyl residues of sugar or GDP and amino residues of lysine or arginine that constitutes protein molecules is shown as formula (2).

As one of the means for the solution of this problem, the modification of heat sterilization conditions for the dialysate has been proposed, but it can not prohibit the protein cross linking completely, and cross-linking reaction of protein by glucose itself may not be disregarded. So that effective prohibition means of protein cross linking are required for peritoneal dialysis.
The inventors of the present invention has proposed the technology wherein the patient's plasma protein, which is migrated out to dialysate, is recovered from peritoneal dialysis effluent and after the concentration, it is used as an osmotic agent for substituting a part or all of glucose. (Japanese Patent Application Hei 8-150930 and Hei 9-302388). However as long as glucose is used as a portion of osmotic agents, the problem of protein cross linking may not be solved completely.